Critical Limb Ischemia, Peripheral Arterial Occlusive Disease
Conditions
Keywords
Hyaluronan, Bone marrow mononuclear cells
Brief summary
The purpose of this study is to evaluate the safety and efficacy of hyaluronan combined with autologous bone marrow mononuclear cells for the treatment of critical PAOD patients.
Detailed description
This is a multicenter, non-blinded and randomized study to evaluate the safety and efficacy of hyaluronan (HA) combined with autologous bone marrow mononuclear cells (BMMNC) therapy for critical peripheral arterial occlusive disease (PAOD) patients. A total of 30 subjects will be recruited into the study. The subjects will be randomized into 3 different arms. During the Phase I study, 9 subjects recruited while another 21 additional subjects will be recruited in Phase II after the review of DSMB and consultation of Taiwan FDA on the results of the Phase I study. Each subject will be administered 5\ 10 injections of RV-P1501, the number of injections depends on the size of the subject's ischemic leg. Each subject will receive treatment once. Subjects will be assigned to the treatments in random order. Evaluations including ABI, PWT/PFWT, clinical status, EF, CTA, biochemistry and hematology checked during the inclusion and exclusion evaluation, and will be taken at baseline, 1 week, 2 weeks, 4 weeks, 12 weeks, and 24 weeks after the treatment.
Interventions
BIOLOGICALRV-P1501
Gel-like product with BMMNCs in each ml of hyaluronan (HA) solution
Sponsors
National Taiwan University Hospital
National Cheng-Kung University Hospital
Academia Sinica, Taiwan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
RV-P1501-4: Gel-like product with 10 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution RV-P1501-5: Gel-like product with 100 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution RV-P1501-6: Gel-like product with 1 million BMMNCs in each ml of 1% hyaluronan (HA) solution
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient age ≥ 20 * Patients with severe PAOD and diagnosed with Rutherford category 3, 4, or 5 * Contraindication to angioplasty or bypass surgery, or post-angioplasty or bypass surgery for once but with limited or no effect. * Patient without hypertension or hypertensive patient with adequate-controlled blood pressure. * With signed informed consent
Exclusion criteria
* Patient undergone any organ transplantation * Inability to undergo bone marrow aspiration * Pregnant woman * Life expectancy \< 1 year * Cognitive impairment * Active malignancy in 5 years prior to treatment * Bleeding diathesis or pulmonary embolism * Patient with active major cardiovascular diseases such as unstable angina, arrhythmia, heart failure, impaired cardiac function (ejection fraction \< 45%), or stroke * Estimated Glomerular Filtration Rate (eGFR) \< 30 * Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) values higher than 80 U/L * Patient with severe diabetes mellitus (HbA1C \> 8%) * Patient with alcohol addiction * Patient with drug abuse * Patient with infections or skin disease on the ischemic leg. * Allergic to HA * Patient whose blockage region only occurred in the femoral artery or at foot.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ankle Brachial Index (ABI) | Day 0, Week 4, Week 12, Week 24 | The percentage change of ABI from 3 follow-ups with the baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of pain at rest | Day 0, Week 1, Week 2, Week 4, Week 12, Week 24 | Rest pain was measured using Wong-Baker FACES pain rating scale at baseline and each follow-up visit. |
| Ulcer size in cm2 | Day 0, Week 1, Week 2, Week 4, Week 12, Week 24 | Ulcer size was assessed and measured at each follow-up interval and compared to baseline. |
| Ulcer category | Day 0, Week 1, Week 2, Week 4, Week 12, Week 24 | Ulcer status was assessed at each follow-up interval and compared to baseline. |
| PWT/PFWT in seconds | Day 0, Week 4, Week 12, Week 24 | Peak walking time and pain-free walking time was measured at baseline and compared to W4, W12 and W24 by treadmill walking tests. |
| Clinical status (Rutherford category) | Day 0, Week 1, Week 2, Week 4, Week 12, Week 24 | Improvement in Rutherford scale was recorded at baseline and each follow-up. |
| Ejection fraction | Week 12, Week 24 | Ejection fraction was measured by echocardiogram to record the cardiac function at W12 and W24. |
| CT angiography | Week 12, Week 24 | CT angiography was performed to record the morphology of blood vessel, location, and the vessel cross section percentage. |
| Biochemistry | Week 12, Week 24 | Biochemistry tests were performed to interpret the health assessment at W12 and W24. |
| Hematology | Week 12, Week 24 | Hematology tests were performed to interpret the health assessment at W12 and W24. |
| Amputation free | Week 1, Week 2, Week 4, Week 12, Week 24 | Time to below the knee amputation of the ipsilateral leg after the treatment. |
Countries
Taiwan
Outcome results
None listed